2BXE

Human serum albumin complexed with diflunisal

Summary for 2BXE

• Entry DOI: 10.2210/pdb2bxe/pdb
• Related: 2BX8 2BXA 2BXB 2BXC 2BXD 2BXF 2BXG 2BXH 2BXI 2BXK 2BXL 2BXM 2BXN 2BXO 2BXP 2BXQ
• Descriptor: SERUM ALBUMIN, 5-(2,4-DIFLUOROPHENYL)-2-HYDROXY-BENZOIC ACID (2 entities in total)
• Functional Keywords: transport protein, carrier protein, lipid-binding, metal-binding, drug-binding
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted: P02768
• Total number of polymer chains: 2
• Total formula weight: 134643.63

Authors

Ghuman, J.,Zunszain, P.A.,Petitpas, I.,Bhattacharya, A.A.,Curry, S. (deposition date: 2005-07-26, release date: 2005-09-22, Last modification date: 2023-12-13)

Primary citation

Ghuman, J.,Zunszain, P.A.,Petitpas, I.,Bhattacharya, A.A.,Otagiri, M.,Curry, S.
Structural Basis of the Drug-Binding Specificity of Human Serum Albumin.
J.Mol.Biol., 353:38-, 2005

PubMed Abstract: Human serum albumin (HSA) is an abundant plasma protein that binds a remarkably wide range of drugs, thereby restricting their free, active concentrations. The problem of overcoming the binding affinity of lead compounds for HSA represents a major challenge in drug development. Crystallographic analysis of 17 different complexes of HSA with a wide variety of drugs and small-molecule toxins reveals the precise architecture of the two primary drug-binding sites on the protein, identifying residues that are key determinants of binding specificity and illuminating the capacity of both pockets for flexible accommodation. Numerous secondary binding sites for drugs distributed across the protein have also been identified. The binding of fatty acids, the primary physiological ligand for the protein, is shown to alter the polarity and increase the volume of drug site 1. These results clarify the interpretation of accumulated drug binding data and provide a valuable template for design efforts to modulate the interaction with HSA.

PubMed: 16169013
DOI: 10.1016/J.JMB.2005.07.075

Experimental method

X-RAY DIFFRACTION (2.95 Å)